The objectives of this research ar to provide reliable information on the therapeutic merits of new and established analgestic drugs which may or do have substantial drug abuse potential (or may be effectively substituted for those that do have abuse potential in controlling moderate to severe pain), and to determine how pharmacokinetic biotransformation data may enable us to predict, or provide, more precise estimates of analgesic efficacy and of the liability of adverse drug reactions. To this end, we propose to carry out controlled clinical analgesic assays in patients with postoperative pain or chronic pain due to cancer in which the measurement of drug concentrations in biofluids will be carried concurrently. The studies will also be desgined to address problems of measuring pain and analgesia in the clinical setting and in ways of improving the efficiency of clinical analgesis assays. Both graded single dose crossover experiments and repeated dose crossover studies are planned of heroin and its active metabolites, 6-monoacetylmorphine and morphine, and of levo-alpha-acetylmethadol (LAAM) and its metabolites, noracetylmethadol (NAM) and dinoracetylmethadol (DNAM). Pharmacokinetic-pharmacodynamic models will be developed to describe the relative contributions of the parent drugs and of the individual metabolites to the observed pharmacologic effects of the drugs. We wish to determine whether, by correspondence analysis of our past analgesic study data and that of our proposed analgesic studies, we can gain better insight into how our categorical analgesic scales are interpreted by patients with self-limiting postoperative pain and patients with intractable pain due to cancer.